Circadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

生物钟协调哺乳动物的行为和生理机能，使生物体能够预测 24 小时周期。转录-翻译反馈环被认为驱动大多数哺乳动物细胞中的这些时钟。然而，红细胞（RBC）不含细胞核，无法进行转录或翻译，但仍表现出昼夜氧化还原节律。在这里，我们展示了人类红细胞对葡萄糖代谢的昼夜节律调节，这是维持每日氧化还原振荡所必需的。我们发现了代谢物水平的每日节律以及通过糖酵解和磷酸戊糖途径（PPP）的通量。我们发现，抑制任一途径中的关键酶都会消除代谢通量和氧化还原振荡的 24 小时节律，并确定代谢振荡对于氧化还原节律是必要的。此外，代谢通量节律也出现在有核细胞中，并且当Bmal1敲除中缺乏核心转录昼夜节律时钟时，代谢通量节律持续存在。因此，我们认为节律性葡萄糖代谢是昼夜节律中不可或缺的过程。